Effect of Chronic Deep Brain Stimulation of the Subthalamic Nucleus for Frontal Lobe Epilepsy: Subtraction SPECT Analysis

Abstract

OBJECTIVES: Experimental data and case reports of patients with intractable epilepsy treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) suggest a considerable anticonvulsant effect. However, no satisfactory mechanisms of action have yet been elucidated. We investigated the putative therapeutic mechanisms of DBS from cerebral perfusion changes as measured by subtracting the SPECT image of the pre-DBS period from that of the chronic post-DBS state. METHODS: Two patients who had previous resective surgery on their right frontal cortices with or without anterior callosotomy were selected for DBS of the STN. Both of them showed frequent bilateral asymmetric tonic seizures (left > right) with rare drop attacks, and 1 patient's seizure frequency was more than 15/month during the pre-DBS period. They had both taken more than four antiepileptic agents for more than 10 years. After video-EEG monitoring, the irritative zones of the brain were delineated. The regional cerebral blood flow (rCBF) changes between the two SPECT images (pre-DBS and post-DBS after at least 6 months) were analyzed by SPECT subtraction with the volumetric MRI coregistration method using Analyze 5.0 software. RESULTS: After chronic STN DBS (18 months, case 1; 6 months, case 2), both patients experienced markedly reduced seizure frequencies (86.7% reduction in patient 1, 88.6% in patient 2). In patient 1, the increased rCBF was observed in the right frontal areas (dorsolateral and inferior frontal area), which corresponded to the irritative zones as confirmed by previous EEG recording. Unexpectedly, there was definite hyperperfusion in the right superior and inferior temporal areas as well as rCBF increase in the right superior frontal area (SMA) in patient 2. CONCLUSIONS: We demonstrated that the cerebral perfusion increase in the irritative zones of epilepsy patients is associated with favorable seizure reduction after STN DBS in 2 cases of frontal lobe epilepsy. Although the exact mechanism remains unknown, our findings suggest that the perfusion changes after STN DBS in frontal lobe epilepsy patients are quite different from those in subjects with Parkinson's disease. Our preliminary data suggest the clinical relevance of subtraction SPECT imaging in assessing the postprocedural outcome as well as the characteristics of SPECT perfusion patterns in other epilepsy syndromes.